Homeostasis of a body fluid is significantly impaired by the rapid accumulation of toxins or pathogens from diseases such as acute cardiac failure, acute renal failure, acute hepatic failure, postoperative hepatic failure, sepsis, burn, toxicosis, fulminant hepatitis and acute pancreatitis. For treatment of the exacerbation of such acute or chronic diseases, the acute blood purification therapy is applied thereto, because it is required to purify the blood and/or body fluid urgently so as to maintain the homeostasis and ameliorate the pathological condition.
The acute blood purification therapy is a blood purification method experientially developed mainly in the critical care/intensive care field, which removes unnecessary or toxic substances from bloods by dialysis, filtration, adsorption or separation (Non-Patent Reference 1).
A specific method for the acute blood purification therapy comprises blood purification by an extracorporeal circulation of blood such as continuous hemodialysis (CHD), continuous hemofiltration (CHF), continuous hemodiafiltration (CHDF), hemodialysis (HD), hemoadsorption (HA), plasma adsorption (PA), plasma exchange (PE) or leukocytapheresis (LC). In these days, CHDF and PE are predominant due to the expansion of their application, the progress of the pathology resolution, etc. (Non-Patent Reference 2).
In the acute blood purification therapy, the use of a huge volume of dialysate or substitute liquid is required for removal of detrimental substances by utilization of the principle of diffusion, ultrafiltration, microfiltration, adsorption or the like.
The essential requirements for the dialysate or substitute liquid to be used in the acute blood purification therapy are as follows: (1) unnecessary or surplus substances are reduced; (2) essential or insufficient substances are supplemented; (3) detrimental substances are undetectable or low enough to cause no problem; (4) essential substances in a body are not reduced below normal concentrations; (5) metabolic substances taken up into a body are not so much as causing a burden to the metabolic pathway; (6) osmotic pressure is close to that of blood; (7) stability is kept and handling is easy, etc. As the dialysate or substitution liquid presently used in the acute blood purification therapy, there are exemplified dialysates for artificial kidneys (e.g. Kindaly®Solution; Fuso Pharmaceutical Industries, Inc.) and substitution liquids for filtration type artificial kidneys (e.g. Sublood®-B, Sublood®-BS; Fuso Pharmaceutical Industries, Inc.) which are sold in the market for the therapy of chronic renal failure, because those meet said requirements and are easily available.
Many of these dialysates and substitution liquids contain sodium bicarbonate. Therefore, the reaction of calcium and magnesium ions with bicarbonate ion therein proceeds with the lapse of time to form insoluble fine particles or precipitates of carbonates. In order to avoid this problem, those are supplied as a kit formulation comprising a solution containing calcium ion (Ca2+) and magnesium ion (Mg2+) (hereinafter referred to as “Solution B”) and a solution containing bicarbonate ion (HCO3−) (hereinafter referred to as “Solution A”, which are kept separately and mixed together on use (Patent Reference 1).
Patent Reference 1: JP-A-2005-28108;                Non-Patent Reference 1: Critical care/intensive care, Vol. 18, No. 1.2:3-4, 2006 (Japanese Journal);        Non-Patent Reference 2: Japanese Journal of Clinical Medicine, Vol. 62 (Supp.):397-402, 2004.        
An example of the dialysate or substitution liquid commercially available comprises sodium ion (Na+), 132-143 mEq/L; potassium ion (K+), 2.0-2.5 mEq/L; calcium ion (Ca2+), 2.5-3.5 mEq/L; magnesium ion (Mg2+), to −1.5 mEq/L; chloride ion (Cl−), 104-114.5 mEq/L; bicarbonate ion (HCO3−), 0-35.0 mEq/L; acetate ion (CH3COO−), 3.5-40 mEq/L; and glucose, 0-200 mg/dL.
For instance, said Sublood®-BS comprises a double chambered container having an upper chamber and a lower chamber separated with a separation wall, the upper and lower chambers containing respectively the following Solutions B and A:
Solution B comprising the following compounds in a volume of 1010 mL (pH, 3.8-3.9; osmotic pressure ratio, 0.9-1.0): sodium chloride (NaCl), 7.88 g; calcium chloride (CaCl2. 2H2O), 519.8 mg; magnesium chloride (MgCl2.6H2O), 205.4 mg; sodium acetate (CH3COONa), 82.8 mg; glucose (C6H12O6), 2.02 g; and glacial acetic acid (CH3COOH), 360.0 mg; and
Solution A comprising the following compounds in a volume of 1010 mL (pH, 7.9-8.5; osmotic pressure ratio, 0.9-1.0): sodium chloride (NaCl), 4.460 g; potassium chloride (KCl), 0.30 g; and sodium bicarbonate ((NaHCO3), 5.940 g.
On the use, the separation wall is broken to communicate the upper and lower chambers and combine Solutions A and B together, and the resultant mixture is administered from the side of the lower chamber. The double chambered container as above is used for keeping separately such active components which are expected to be reacted in the coexistence of them as bicarbonate ion and calcium and/or magnesium ions.
Other examples of the drug solution comprising bicarbonate ion are peritoneal dialysate, bicarbonate Ringer's solution, high calorie transfusion, etc., and most of them also keep bicarbonate ion and calcium and/or magnesium ions separately by accommodating them in a double chambered container in order to avoid the reaction between them (cf. JP-A-11-197240, etc.).